Despite the use of new antiviral drugs, herpes simplex (HSV) continues to be the infectious agent responsible for most corneal blindness in the United States. Several line of evidence indicate the HSV produces blindness mainly by immunologically induced corneal scarring. HSV's tendency to recur appears to be under immunological control as well. Therefore, altering the immune response to HSV could have a significant effect on ocular herpes scarring and recurrences. Augmentation of this ocular immune response will be produced as a byproduct of using systemic HSV vaccines. Several such candidate vaccines are under development for human use to protect a large sexually active population against genital herpes. Surprisingly, there have been no laboratory or clinical studies to determine whether these vaccines might induce deleterious (or beneficial) effects on immunologically mediated herpetic eye disease and ocular HSV recurrence. This proposal specifically aims to address the crucial public health questions regarding the ocular safety and effects of systemic HSV vaccines. It will assess the ocular dangers and benefits of vaccination with HSV vaccines which are candidates for human use. Using experimental animal models, which mirror human HSV corneal scarring and recurrence, the project will investigate: 1) the effect of the severity of subsequently induced and of pre-existing stromal keratitis; 2) the effect of prior vaccine use in protecting animals from developing latent ocular HSV infections; 3) whether in animals with latent infections, vaccination decreases HSV reactivation and clinical recurrences. The study will also set standards by which to test new candidate vaccines that will be developed. Additionally, early topical antiviral chemotherapy, which appears to be a promising means to stop the development of HSV stromal keratitis will be studied in detail. The long-term objective of this proposal is to lessen HSV corneal blindness by discovering means to ameliorate the two remaining ocular herpes problems, stromal scarring and recurrence. This proposal promises to generate significant advances in controlling both.